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Study Title and Description

Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis.



Key Questions Addressed
1 How are the efficacy and safety of corticosteroid implants for chronic non-infectious uveitis?
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Primary Publication Information
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TitleData
Title Evaluation of an intravitreal fluocinolone acetonide implant versus standard systemic therapy in noninfectious posterior uveitis.
Author Pavesio C., Zierhut M., Bairi K., Comstock TL., Usner DW.
Country Medical Retina Service/Moorfields Eye Hospital, London, UK. carlos.pavesio@moorfields.nhs.uk
Year 2010
Numbers Pubmed ID: 20079922

Secondary Publication Information
There are currently no secondary publications defined for this study.


Extraction Form: Corticosteroid implants for chronic non-infectious uveitis 2016
Arms
Number Title Description Comments
1 Fluocinolone acetonide surgical implantation of 0.59 mg FA in vitreous cavity
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2 Standard-of-care standard-of-care systemic management of uveitis
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Design Details
Question... Follow Up Answer Follow-up Answer
Page 567-75
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Study design parallel-group, randomized controlled trial
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Number randomized
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Total 146 participants
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FA implant group 72 participants
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Standard-of-care group 74 participants
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Number analyzed
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Total_1 140 participants
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FA implant group_1 66 participants
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Standard-of-care group_1 74 participants
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Exclusions and loss to follow-up 6 treatment group participants excluded due to administrative problems (3), consent withdrawal (2), adverse events (1)
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Total_2
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FA implant group_2 40.4 +/- 14.4 years, 12 to 75 years
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Standard-of-care group_2 43.1 +/- 13.5 years, 18 to 70 years
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Study follow-up 24 months
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Country
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Age (mean +/- SD, range)
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Gender
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Overall not reported
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Women 85/146 participants (58.2%);
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Men 61/146 participants (41.8%)
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By group
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Inclusion criteria [if this is copied text, need quotes]"Quiet eyes at the time of treatment. Only eye randomized to implant had to be quiet at the time of surgery. Treatment with either greater than or equal to 0.2 mg/kg daily prednisolone equivalent or greater than or equal to 0.1 mg/kg daily prednisolone equivalent immunosuppressant at the time of randomization was required.Male or non-pregnant female aged greater than or equal to 6 yearsgreater than or equal to 1-year history of recurrent or recrudescent unilateral or asymmetric NIPU not associated with significant systemic activity of any underlying diseaseMore severely affected eyes with greater than or equal to 2 separate recurrences of NIPU and the last episode occurring within 8 months of enrolment
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Exclusion criteria [if this is copied text, need quotes]"History of retinal detachment, retinoschisis in the area of implantationMedia opacity precluding evaluation of the retina and vitreousPresence or history of uncontrolled IOP while receiving steroid therapy resulting in loss of visionIOP > 25 mmHg requiring at least 2 antiglaucoma medications to be reduced to < 25 mmHgKnown allergy or contraindication to fluocinolone acetonide, systemic corticosteroids, or immunosuppressive agentsChronic use of such agents to manage nonocular diseaseHistory of NIPU only or iritis only with no vitreitis, macular edema, vitreous cells, or vitreous hazeInfectious causeVitreous haemorrhage or a toxoplasma scar in the study eyeOcular surgery, trauma affecting the study eye, or both within 3 months before enrolment, or trabeculoplasty or yttrium&ndash;aluminum&ndash;garnet laser within 1 month of enrolmentMonocularity for reasons other than uveitisPositive human immunodeficiency virus test results, pregnancy or lactationPotential for noncompliance, or participation in other clinical studies within 1 month of enrolment"
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5. Advanced glaucomatous optic nerve injury meeting the following criteria
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Participants with unilateral and asymmetric bilateral disease were included For participants with unilateral disease, the affected eye was the study eye. For participants with asymmetric bilateral disease, the study eye was the more severely affected eye.
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FA implant surgical implantation of 0.59 mg FA in vitreous cavity
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Standard-of-care standard-of-care systemic management of uveitis"The SOC group received prednisolone or an equivalent corticosteroid alone, or an immunosuppressive agent was added to the therapy and the corticosteroid dose was reduced. Levels considered acceptable for therapy with steroids alone were 0.2 mg/kg daily (or 15 mg/day for the average weight). When inflammation could not be controlled with this level of corticosteroid, immunosuppressive agents were added. With the use of an immunosuppressive agent, the objective was to reduce steroid use to 0.1 mg/kg daily of prednisolone equivalent after 4 to 6 weeks of combination therapy. Approved immunosuppressants included cyclosporine A, methotrexate, cyclophosphamide, mycophenolate mofetil, azathioprine, and tacrolimus. If an immunosuppressive agent was not recommended, subjects were managed by maintaining systemic steroids at a higher level (0.2 mg/kg daily of prednisolone equivalent) or by increasing the steroids in case of inflammation. This regimen was followed by a slow taper to a minimal dose of 0.2 mg/kg daily (10 mg/day for subjects whose weight was 50 kg). After 6 months, if the disease was controlled, the treatment doses were tapered according to the standard guideline of each investigational site." P569
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General procedures ophthalmic examination
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Primary outcome
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Secondary outcome(s)
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Other outcomes(s)
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Measurements taken
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Unit of analysis individual (one eye per participant)
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Sample size calculation "A sample size of 75 subjects per treatment was determined to have 85% power to detect a difference with respect to the primary end point in a 2-tailed test (0.05)."
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Study dates April 2002 through August 2005
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Funding sources
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Declaration of interest Of the 5 study authors, lead author is a consult for Bausch and Lomb Inc, and 3 authors are employees of Bausch and Lomb Inc.
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Trial registry not registered
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Publication language English
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Number analyzed at 24 months' follow-up
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Countries France, Germany, Israel, Italy, Portugal, Saudi Arabia, Spain, Switzerland, Turkey, United Kingdom
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Overall_1
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FA implant group_3
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Women_1 35/72 participants (48.5%);
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Men_1 37/72 participants (51.5%)
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Standard-of-care group_3
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Women_2 50/74 participants (67.6%)
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Men_2 24/74 participants (32.4%)
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More severely affected eyes were treated with systemic therapy for greater than or equal to 1 month greater than or equal to 0.2 mg/kg daily prednisolone equivalent (greater than or equal to 10 mg/kg daily for participants > 50 kg) or greater than or equal to 0.1 mg/kg daily prednisolone equivalent if steroids were given with &frac12; of the following immunosuppressive agents:cyclosporine A, methotrexatecyclophosphamide, tacrolimusmycophenolate mofetil, azathioprine
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Less severely affected eyes with VA of greater than or equal to 0.7 logMAR (6/30)Uveitis requiring only periocular injections or no therapy
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Study eyes at time of enrolment VA of greater than or equal to 1.4 logMAR (6/150)less than or equal to 10 anterior chamber cells/high-power field and a vitreous haze grade less than or equal to 2"
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Primary outcomes time to first recurrence of uveitis occurring in the 24 months after randomization for the standard-of-care group and time to first recurrence of uveitis in the study eye in the 24 months after the week 12 visit for the implant group
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Secondary outcomes Percentage of participants with at least 1 recurrenceNumber of recurrences per participantNumber of recurrences compared with the number that occurred during the 52 weeks before enrollmentProportion of participants with a VA improvement (> 15 letters on Early Treatment Diabetic Retinopathy Study charts from baseline)If cystoid macular edema present, the change in the size of the area of cystoid macular edema on fluorescein angiography
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Measurements taken, specify intervals at which outcomes assessed Participants were assessed monthly for 3 months, bimonthly for 6 months, and then every 3 months for the second year of the study.
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Funding source Bausch and Lomb Inc
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Random sequence generation (selection bias):Authors' judgement Low risk
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Random sequence generation (selection bias):Support for judgement &";Subjects were allocated to receive either an implant or standardized therapy as determined by a randomization code with treatment randomization numbers assigned by a centrally administered randomization procedure.&"; P569
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Allocation concealment (selection bias):Authors' judgement Low risk
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Allocation concealment (selection bias):Support for judgement &";Treatment allocation was masked to both the investigator and the subject through the use of an interactive voice response system that informed the investigator of the treatment group only after confirmation of inclusion of the subject.&"; P569
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Masking of participants and personnel (performance bias):Authors' judgement High risk
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Masking of participants and personnel (performance bias):Support for judgement The study was designed to assess surgical implant vs standard-of-care oral therapy. &";... it was not possible to mask study treatments ...&"; P569
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Masking of outcome assessment (detection bias):Authors' judgement High risk
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Masking of outcome assessment (detection bias):Support for judgement No masking for primary outcomes. For secondary outcomes: &";... some assessments, including fluorescein angiography, fundus photography, and laboratory parameters, were masked.&"; P569
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Incomplete outcome data (attrition bias):Authors' judgement Unclear risk
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Incomplete outcome data (attrition bias):Support for judgement &";Six subjects randomized to the FA implant group discontinued before receiving treatment because of administrative problems, consent withdrawal, or AEs and were excluded from the intent-to-treat population.&"; P570. Data for all other participants was included. &";All randomized subjects who underwent at least 1 assessment after randomization were included in the intent-to-treat population, and all efficacy and safety summaries were based on the intent-to-treat populations. Data from the per-protocol population also were analyzed for most outcome measures.&"; P570
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Selective reporting (reporting bias):Authors' judgement Unclear risk
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Selective reporting (reporting bias):Support for judgement Study protocol and trial registry were not available for comparison. All of the prespecified outcomes from the methods section were reported in the results section
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Other bias:Authors' judgement High risk
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Other bias:Support for judgement Several of the authors are employees of the sponsor, and the lead author is a consultant for the sponsor. There is no statement about the role of the sponsor in study design, data analysis, interpretation, decision to publish, or manuscript preparation
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Results & Comparisons


Results Data
Outcome: Proportion of participants with a recurrence of uveitis      Population: All Participants
Time Point Measure Fluocinolone acetonide Standard-of-care


24 months

N Analyzed 61 eyes 71 eyes
Unit 38% (23 out of 61 eyes) 68% (48 out of 71 eyes)

Adverse Events
Arm or Total Title Description Proportion of adverse events Comments
Fluocinolone acetonide cataract formation or progression through 24 months 44/49
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Standard-of-care 13/57
Fluocinolone acetonide retinal tear or retinal detachment through 24 months 1/66
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Standard-of-care 2/74
Fluocinolone acetonide endophthalmitis through 24 months 3/66
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Standard-of-care 0/74
Fluocinolone acetonide elevated intraocular pressure > 10 mmHg through 24 months 37/66
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Standard-of-care 8/74
Fluocinolone acetonide cataract surgery through 24 months 43/49
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Standard-of-care 11/57
Fluocinolone acetonide IOP-lowering surgery through 24 months 14/66
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Standard-of-care 2/74
Fluocinolone acetonide Hypotony through 24 months 13/66
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Standard-of-care 1/74